Cholinergic muscarinic M1 and M4 receptors as therapeutic targets for cognitive, behavioural, and psychological symptoms in psychiatric and neurological disorders

Drug Discov Today. 2019 Dec;24(12):2307-2314. doi: 10.1016/j.drudis.2019.08.009. Epub 2019 Sep 6.

Abstract

Cholinergic dysfunction is involved in a range of neurological and psychiatric disorders, including schizophrenia, dementia and Lewy body disease (LBD), leading to widespread use of cholinergic therapies. However, such drugs have focused on increasing the availability of acetylcholine (ACh) generally, with relatively little work done on the muscarinic system and specific muscarinic receptor subtypes. In this review, we provide an overview of the major cholinergic pathways and cholinergic muscarinic receptors in the human brain and evidence for their dysfunction in several neurological and psychiatric disorders. We discuss how the selectivity of cholinergic system dysfunction suggests that targeted cholinergic therapeutics to the muscarinic receptor subtypes will be vital in treating several disorders associated with cognitive dysfunction and behavioural and psychological symptoms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / physiopathology
  • Drug Development
  • Humans
  • Mental Disorders / drug therapy
  • Mental Disorders / physiopathology*
  • Molecular Targeted Therapy
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / physiopathology*
  • Receptor, Muscarinic M1 / metabolism*
  • Receptor, Muscarinic M4 / metabolism*

Substances

  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M4
  • Acetylcholine